Inflammation often is a bodily response to infection or injury in which cells involved in detoxification and repair are mobilized to the compromised site by inflammatory mediators. The infection or injury can result from any of a variety of causes including acute or chronic disease, disorders or conditions; trauma, environmental conditions, or aging. For example, inflammation may result from diseases, disorders, syndromes, conditions and injuries of the cardiovascular, digestive, integumentary, muscular, nervous, reproductive, respiratory and urinary systems. Representative diseases, disorders or conditions that involve inflammation include atherosclerosis, irritable bowel syndrome, tendonitis, Alzheimer's disease and vascular dementia, multiple sclerosis, diabetes, endometriosis, asthma and kidney failure.
In addition, inflammation may result from diseases, disorders, syndromes, conditions and injuries of cartilage and tissue, including skin. Representative diseases, disorders or conditions involving inflammation of the skin include rosacea, psoriasis, acne, or the like, and include diseases, disorders or conditions which may be exacerbated by the presence or colonization of agents or vectors, such as bacteria.
Difficulties associated with the treatment of conditions related to bacterial colonization of mammalian epithelium are well-appreciated amongst dermatologists. This is particularly true in the case of skin and wound antisepsis, where the most effective treatment of epithelial conditions caused or aggravated by bacterial colonization, often includes the use of a topical anti-bacterial agent.
The emergence of bacterial resistance to commonly-used antibiotics, however, has posed an ever-increasing challenge in the treatment, prevention and containment of epithelial-related conditions, caused or aggravated by bacteria. There is a clear and urgent need for innovative and cost-effective methods for an efficacious treatment, prevention and/or management of such conditions.
Other background and methods may be found in U.S. Pat. Nos. 5,043,268, 5,202,456, 5,705,528; United States Patent Publications: 2005/0277694, 2007/0004803, 2009/0155186, 2009/0170917; World Publication WO 2009/102997, and U.S. Provisional Patent Application 61/113,498, disclosure of each of which is incorporated herein by reference.
N-acetyl-farnesyl-cysteine (“AFC”), also referred to as N-acetyl-5-trans, trans-farnesyl-L-cysteine, is a signal transduction modulator that has been shown to reduce inflammation in mice. AFC is a polyisoprenyl-protein inhibitor, and has been shown to be a competitive inhibitor of membrane-associated isoprenyl-5-cysteinyl methyltransferase. AFC has also been shown to block some neutrophil, macrophage, and platelet responses in vitro. Treatment of inflammatory diseases or disorders with traditional anti-inflammatory drugs, e.g., corticosteroids and non-steroidal anti-inflammatory drugs (“NSAIDS”) can cause multiple side effects, e.g., appetite and weight gain, excess sweating, high blood pressure, nausea, vomiting, diarrhea, etc.
What is needed is a compound advantageously having high anti-inflammatory and/or antibacterial activity for use against a variety of diseases, disorders or conditions.